Anemia with low reticulocytosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Differentiating Anemia with low reticulocytosis from Other Diseases

To review the differential diagnosis of anemia, click here.

Disease	Genetics	Clinical manifestation					Lab findings
		History	Symptoms	Signs	Hemolysis	Intrinsic/Extrinsic	Hb concentration	MCV	RDW	Reticulocytosis	Haptoglobin levels	Hepcidin	Iron studies					Specific finding on blood smear
		History	Symptoms	Signs	Hemolysis	Intrinsic/Extrinsic	Hb concentration	MCV	RDW	Reticulocytosis	Haptoglobin levels	Hepcidin	Serum iron	Serum Tfr level	Transferrin or TIBC	Ferritin	Transferrin saturation	Specific finding on blood smear
Iron deficiency anemia^[1]	−	Menorrhagia GI loss GI surgery Pregnancy	Koilonychia Pica	Glossitis Cheilosis Dysphagia	−	−	Hypochromic	Microcytic	↑	Nl or ↓	Nl	Nl	↓	↑	↑	↓	↓↓↓	Central pallor
Iron deficiency anemia (early phase)^[2]	−	Pica Glossitis Cheilosis	Fatigue Headache	Koilonychia Conjunctival pallor Dry skin	−	−	Normochromic	Normocytic	↑	↓	Nl	Nl	↓	↑	↑	↓	↓	Pencil cells Elliptocytosis Hypochromasia
Lead poisoning^[3]	−	House painted with chipped paint	Burtonian lines Basophilic stippling Wrist drop Foot drop	Wrist drop Foot drop Burtonian lines	−	−	Hypochromic	Microcytic	Nl	Nl or ↓	Nl	Nl	Nl to ↓	Nl	Nl	Nl to ↓	−	RBCs retain aggregates of rRNA Basophilic stippling
Sideroblastic anemia^[4]	Defect in ALA synthase gene Autosomal dominant Autosomal recessive X-linked	Alcohol abuse Isoniazid use Chloramphenicol use Idiopathic	Seborrheic dermatitis Glossy Tongue Tingling	Patient present with symptoms of Vitamin B6, copper deficiency symptoms	−	−	Hypochromic	Microcytic	Nl	Nl or ↓	Nl	Nl	↑	Nl	Nl to ↓	↑	−	Ringed sideroblasts
Disease	Genetics	History	Symptoms	Signs	Hemolysis	Intrinsic/Extrinsic	Hb concentration	MCV	RDW	Reticulocytosis	Haptoglobin levels	Hepcidin	Serum iron	Serum Tfr level	IBC	Ferritin	Transferrin saturation	Specific finding on blood smear
Anemia of chronic disease^[5]	−	Rheumatoid arthritis SLE Neoplasm Chronic kidney disease	Headache Shortness of breath	−	−	−	Hypochromic	Microcytic	Nl	Nl or ↓	Nl	↑	↓	Nl	↓	↑	−	NA
Thalassemia^[6]	α-thalassemia α– globin gene deletions Cis deletions Trans deletions β-thalassemia Point mutation in splice sites and promoter sequences	Associated with parvovirus B19	α-thalassemia Hydrops fetalis β-thalassemia Skeletal deformities Chipmunk facies	Hepatomegaly Splenomegaly	−	−	Hypochromic	Microcytic	Nl	Thalassemia trait: Nl or ↓ Thalassemia Syndromes: ↑	Nl	Nl	Nl to ↑	Nl	Nl	↑	Nl to ↑	Target cells Anisopoikilocytosis
Aplastic anemia^[7]	Constitutive expression of Tbet Mutations in the perforin gene Mutations in SAP gene	Exposure to Radiation Drugs like Benzene, chloramphenicol, alkylating agents Viral infections like EBV, HIV, Hepatitis Fanconi anemia Idiopathic like Immune mediated, primary stem cell defect	Symptoms based on underlying condition	Short stature Cafe-au-lait spots Thumb defects Radial defects	−	−	Normochromic	Normocytic	↑	↓	Nl	Nl	↓	↓	Nl	↑	↓	Pancytopenia Fatty infiltration
Disease	Genetics	History	Symptoms	Signs	Hemolysis	Intrinsic/Extrinsic	Hb concentration	MCV	RDW	Reticulocytosis	Haptoglobin levels	Hepcidin	Serum iron	Serum Tfr level	IBC	Ferritin	Transferrin saturation	Specific finding on blood smear
Folate deficiency^[8]	Impaired DNA synthesis	Alcohol consumption History of using drugs like methotrexate, trimethoprim, and phenytoin Low socioeconomic groups with poor nutrition Older people Pregnant and lactating women	No neurological symptoms vs B12 deficiency Odynophagia Angular stomatitis	Glossitis Signs of heart failure Anencephaly and spina bifida	−	−	Anisochromic	Macrocytic	↑	↓	Nl	Nl	↑	↑	↓	↑	↑	RBC macrocytosis Hypersegmented neutrophils Pancytopenia in severe cases
Vitamin B12 deficiency^[9]	Impaired DNA synthesis	Pernicious anemia Crohn’s disease Gastrectomy Veganism Diphyllobothrium latum infection	Psychosis Insomnia Depression Cognitive slowing Restless leg syndrome	Neurological deficit Myelopathy Memory loss with reduced attention span Nystagmus Positive romberg sign Positive Lhermitte’s sign	−	−	Anisochromic	Macrocytic	↑	↓	Nl	Nl	↑	↑	↓	↑	↑	Senile neutrophil Anisocytosis Ovalocytes
Orotic aciduria^[10]	Autosomal recessive Deficiency of enzyme UMPS	Episodic vomiting Rhabdomyolysis	Coma Gastrointestinal manifestation	Neurological manifestation	−	−	Anisochromic	Macrocytic	↑	↓	Nl	Nl	↑	↑	↓	↑	↑	NA
Disease	Genetics	History	Symptoms	Signs	Hemolysis	Intrinsic/Extrinsic	Hb concentration	MCV	RDW	Reticulocytosis	Haptoglobin levels	Hepcidin	Serum iron	Serum Tfr level	IBC	Ferritin	Transferrin saturation	Specific finding on blood smear
Fanconi anemia^[11]	Autosomal recessive X-linked recessive	History of anemia at age 16	Hypopigmentation Cafe-au-lait patches Radial ray anomaly	Significant for bilateral short thumbs	−	−	Anisochromic	Macrocytic	↑	↓	Nl	Nl	↑	↑	↓	↑	↑	Nl appearing WBC, RBC and Platelets But the number is greatly reduced
Diamond-Blackfan anemia^[12]	Mutations in: RPL5 RPL11 RPL35A RPS7 RPS10 RPS17 RPS19 RPS24 RPS26	Associated with myelodysplastic syndrome Increased risk of AML	Pale skin Sleepiness Heart murmurs	Triphalangeal thumbs Short stature Microcephaly Hypertelorism Ptosis Micrognathia	−	−	Anisochromic	Macrocytic	Nl	↓	Nl	Nl	↑	↑	↓	↑	↑	NA
Infections^[13]	−	Associated with Malaria Babesia	Fever	Fever Signs of shock Headache	+	Extrinsic	Normochromic	Normocytic	↑	↑	↓	Nl	Nl	Nl	−	−	−	Trophozoite Maltese crosses

References

↑ Camaschella C (May 2015). “Iron-deficiency anemia”. N. Engl. J. Med. 372 (19): 1832–43. doi:10.1056/NEJMra1401038. PMID 25946282.
↑ De Andrade Cairo RC, Rodrigues Silva L, Carneiro Bustani N, Ferreira Marques CD (June 2014). “Iron deficiency anemia in adolescents; a literature review”. Nutr Hosp. 29 (6): 1240–9. doi:10.3305/nh.2014.29.6.7245. PMID 24972460.
↑ Bain BJ (December 2014). “Lead poisoning”. Am. J. Hematol. 89 (12): 1141. doi:10.1002/ajh.23852. PMID 25220013.
↑ Bottomley SS, Fleming MD (August 2014). “Sideroblastic anemia: diagnosis and management”. Hematol. Oncol. Clin. North Am. 28 (4): 653–70, v. doi:10.1016/j.hoc.2014.04.008. PMID 25064706.
↑ Roy CN (2010). “Anemia of inflammation”. Hematology Am Soc Hematol Educ Program. 2010: 276–80. doi:10.1182/asheducation-2010.1.276. PMID 21239806.
↑ Zainal NZ, Alauddin H, Ahmad S, Hussin NH (December 2014). “α-Thalassemia with Haemoglobin Adana mutation: prenatal diagnosis”. Malays J Pathol. 36 (3): 207–11. PMID 25500521.
↑ Dolberg OJ, Levy Y (2014). “Idiopathic aplastic anemia: diagnosis and classification”. Autoimmun Rev. 13 (4–5): 569–73. doi:10.1016/j.autrev.2014.01.014. PMID 24424170.
↑ Koike H, Takahashi M, Ohyama K, Hashimoto R, Kawagashira Y, Iijima M, Katsuno M, Doi H, Tanaka F, Sobue G (March 2015). “Clinicopathologic features of folate-deficiency neuropathy”. Neurology. 84 (10): 1026–33. doi:10.1212/WNL.0000000000001343. PMID 25663227.
↑ Hunt A, Harrington D, Robinson S (September 2014). “Vitamin B12 deficiency”. BMJ. 349: g5226. PMID 25189324.
↑ Grohmann K, Lauffer H, Lauenstein P, Hoffmann GF, Seidlitz G (April 2015). “Hereditary orotic aciduria with epilepsy and without megaloblastic anemia”. Neuropediatrics. 46 (2): 123–5. doi:10.1055/s-0035-1547341. PMID 25757096.
↑ Alter BP (2014). “Fanconi anemia and the development of leukemia”. Best Pract Res Clin Haematol. 27 (3–4): 214–21. doi:10.1016/j.beha.2014.10.002. PMC 4254647. PMID 25455269.
↑ Vlachos A, Blanc L, Lipton JM (June 2014). “Diamond Blackfan anemia: a model for the translational approach to understanding human disease”. Expert Rev Hematol. 7 (3): 359–72. doi:10.1586/17474086.2014.897923. PMID 24665981.
↑ Bustinduy AL, Parraga IM, Thomas CL, Mungai PL, Mutuku F, Muchiri EM, Kitron U, King CH (March 2013). “Impact of polyparasitic infections on anemia and undernutrition among Kenyan children living in a Schistosoma haematobium-endemic area”. Am. J. Trop. Med. Hyg. 88 (3): 433–40. doi:10.4269/ajtmh.12-0552. PMC 3592521. PMID 23324217.

[pmid25946282-1] Camaschella C (May 2015). “Iron-deficiency anemia”. N. Engl. J. Med. 372 (19): 1832–43. doi:10.1056/NEJMra1401038. PMID 25946282.

[pmid24972460-2] De Andrade Cairo RC, Rodrigues Silva L, Carneiro Bustani N, Ferreira Marques CD (June 2014). “Iron deficiency anemia in adolescents; a literature review”. Nutr Hosp. 29 (6): 1240–9. doi:10.3305/nh.2014.29.6.7245. PMID 24972460.

[pmid25220013-3] Bain BJ (December 2014). “Lead poisoning”. Am. J. Hematol. 89 (12): 1141. doi:10.1002/ajh.23852. PMID 25220013.

[pmid25064706-4] Bottomley SS, Fleming MD (August 2014). “Sideroblastic anemia: diagnosis and management”. Hematol. Oncol. Clin. North Am. 28 (4): 653–70, v. doi:10.1016/j.hoc.2014.04.008. PMID 25064706.

[pmid21239806-5] Roy CN (2010). “Anemia of inflammation”. Hematology Am Soc Hematol Educ Program. 2010: 276–80. doi:10.1182/asheducation-2010.1.276. PMID 21239806.

[pmid25500521-6] Zainal NZ, Alauddin H, Ahmad S, Hussin NH (December 2014). “α-Thalassemia with Haemoglobin Adana mutation: prenatal diagnosis”. Malays J Pathol. 36 (3): 207–11. PMID 25500521.

[pmid24424170-7] Dolberg OJ, Levy Y (2014). “Idiopathic aplastic anemia: diagnosis and classification”. Autoimmun Rev. 13 (4–5): 569–73. doi:10.1016/j.autrev.2014.01.014. PMID 24424170.

[pmid25663227-8] Koike H, Takahashi M, Ohyama K, Hashimoto R, Kawagashira Y, Iijima M, Katsuno M, Doi H, Tanaka F, Sobue G (March 2015). “Clinicopathologic features of folate-deficiency neuropathy”. Neurology. 84 (10): 1026–33. doi:10.1212/WNL.0000000000001343. PMID 25663227.

[pmid25189324-9] Hunt A, Harrington D, Robinson S (September 2014). “Vitamin B12 deficiency”. BMJ. 349: g5226. PMID 25189324.

[pmid25757096-10] Grohmann K, Lauffer H, Lauenstein P, Hoffmann GF, Seidlitz G (April 2015). “Hereditary orotic aciduria with epilepsy and without megaloblastic anemia”. Neuropediatrics. 46 (2): 123–5. doi:10.1055/s-0035-1547341. PMID 25757096.

[pmid25455269-11] Alter BP (2014). “Fanconi anemia and the development of leukemia”. Best Pract Res Clin Haematol. 27 (3–4): 214–21. doi:10.1016/j.beha.2014.10.002. PMC 4254647. PMID 25455269.

[pmid24665981-12] Vlachos A, Blanc L, Lipton JM (June 2014). “Diamond Blackfan anemia: a model for the translational approach to understanding human disease”. Expert Rev Hematol. 7 (3): 359–72. doi:10.1586/17474086.2014.897923. PMID 24665981.

[pmid23324217-13] Bustinduy AL, Parraga IM, Thomas CL, Mungai PL, Mutuku F, Muchiri EM, Kitron U, King CH (March 2013). “Impact of polyparasitic infections on anemia and undernutrition among Kenyan children living in a Schistosoma haematobium-endemic area”. Am. J. Trop. Med. Hyg. 88 (3): 433–40. doi:10.4269/ajtmh.12-0552. PMC 3592521. PMID 23324217.

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